We propose research which will evaluate the effects of experimental coronary-myocardial ishemia on the transcapillary exchange and tissue distribution of radioisotopes. In open-chest dog preparations, the transport effects of mild, moderate and severe ischemia induced by coronary constriction will be measured by single-pass bolus-injection multiple indicator curves. Tracers will be allowed to enter the left anterior descending coronary artery through a cannula. Outflow samples will be collected from the coronary sinus. Ischemia will be produced by constriction or total occlusion of the cannula flow. Several mathematical theories will be used to infer transport properties from these observations. Ischemic effects of transport will be compared to transport changes resulting from infusions of three drugs which may affect capillary-tissue exchange: hyaluronidase, histamine and adenosine. The results will be used to evaluate the diagnostic importance of transport alterations in coronary disease and to suggest targets for therapeutic control of capillary permeability. The effects of changes in capillary permeability and tracer distribution volumes on coronary hemodynamics will be studied.